Ichiro Miwa

Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate

Abstract:  We investigated the relationship between oxidative stress and poor oocyte quality and whether the antioxidant melatonin improves oocyte quality. Follicular fluid was sampled at oocyte retrieval during in vitro fertilization and embryo transfer (IVF‐ET). Intrafollicular concentrations of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) in women with high rates of degenerate oocytes were significantly higher than those with low rates of degenerate oocytes. As there was a negative correlation between intrafollicular concentrations of 8‐OHdG and melatonin, 18 patients undergoing IVF‐ET were given melatonin (3 mg/day), vitamin E (600 mg/day) or both melatonin and vitamin E. Intrafollicular concentrations of 8‐OHdG and hexanoyl‐lysine adduct were significantly reduced by these antioxidant treatments. One hundred and fifteen patients who failed to become pregnant with a low fertilization rate (50%) in the previous IVF‐ET cycle were divided into two groups during the next IVF‐ET procedure; 56 patients with melatonin treatment (3 mg/day) and 59 patients without melatonin treatment. The fertilization rate was improved by melatonin treatment compared to the previous IVF‐ET cycle. However, the fertilization rate was not significantly changed without melatonin treatment. Oocytes recovered from preovulatory follicles in mice were incubated with H2O2 for 12 hr. The percentage of mature oocytes with a first polar body was significantly reduced by addition of H2O2 (300 μm). The inhibitory effect of H2O2 was significantly blocked by simultaneous addition of melatonin. In conclusion, oxidative stress causes toxic effects on oocyte maturation and melatonin protects oocytes from oxidative stress. Melatonin is likely to improve oocyte quality and fertilization rates.

Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium

OBJECTIVE To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow. DESIGN A prospective observational study. SETTING University hospital and city general hospital. PATIENT(S) Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81). INTERVENTION(S) Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given. MAIN OUTCOME MEASURE(S) EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound. RESULT(S) Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium. CONCLUSION(S) Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.

Modified sequential laser photocoagulation of placental communicating vessels for twin–twin transfusion syndrome to prevent fetal demise of the donor twin

Aims:  Twin–twin transfusion syndrome (TTTS) complicated with absent or reversed end‐diastolic flow in the umbilical artery (UA‐AREDF) of the donor has a high perinatal mortality rate. To improve the prenatal outcome, we introduced and modified the technique of sequential selective laser photocoagulation of communicating vessels (SQLPCV), and assessed the clinical efficacy.

Resolution of mirror syndrome after successful fetoscopic laser photocoagulation of communicating placental vessels in severe twin–twin transfusion syndrome

Mirror syndrome, also known as Ballantyne syndrome or triple edema, characterizes maternal edema related to severe fetal hydrops and placental edema. In singleton pregnancies, various etiologies associated with this syndrome have been reported: parvovirus B19 infection (Brochot et al., 2006), fetal arrhythmia (Midgley and Harding, 2000), Rh isoimmunization (Kaiser, 1971), sacrococcygeal teratoma (Livingston et al., 2007), and placental chorioangioma (Dorman and Cardwell, 1995). In multiple pregnancies, hydrops related to twin–twin transfusion syndrome (TTTS) (Hayashi et al., 2006; Chang et al., 2007) can cause mirror syndrome; in some cases, however, the etiology is unknown (Heyborne and Chism, 2000). Several reports have shown that mirror syndrome can be cured provided the hydrops is treated by fetal therapy (Heyborne and Chism, 2000; Midgley and Harding, 2000; Livingston et al., 2007). We report the first case of spontaneous resolution of mirror syndrome after successful fetoscopic laser photocoagulation (FLP) of the communicating placental vessels in TTTS complicated with hydrops fetalis of the recipient twin. A 33-year-old gravida 1, para 0 woman was referred to our hospital at 21 weeks and 3 days of gestation for management of TTTS. She conceived and gestated monochorionic twins after in vitro fertilizationembryo transfer. The monochorionic twin pregnancy was diagnosed by ultrasonography in the referral hospital at an earlier gestational age. Initial ultrasound examination demonstrated polyhydramnios in the recipient’s sac (maximum vertical pocket (MVP), 8.4 cm) and oligohydramnios in the donor’s sac (MVP, 0 cm). Moreover, the recipient twin manifested hydrops fetalis with skin edema, ascites, and pleural effusion complicated with hypertrophic cardiomegaly. A Doppler study revealed pulsatile umbilical venous flow and reverse

Fetoscopic laser photocoagulation of placental communicating vessels for twin-reversed arterial perfusion sequence.

Twin‐reversed arterial perfusion (TRAP) sequence is a rare and compromised complication in monochorionic pregnancies. The retrograde blood flow through placental communicating vessels is mainly involved to develop the syndrome. Increased cardiac output in the pump twin can lead to severe clinical manifestations. Various surgical techniques to occlude vascular communications between the pump twin and acardiac twin have been reported. A woman with TRAP sequence, at 22 weeks of gestation, complicated with progressive polyhydramnios underwent fetoscopic laser photocoagualtion of vascular communications on the placental surface. Fetoscopic observation demonstrated one artery‐to‐artery anastomosis and one venous‐to‐venous anastomosis from the pump twin to the acardiac twin, and these communications were successfully photocoagulated. The patient delivered a 2308‐g female infant at 34 weeks and 1 day of gestation, following premature rupture of membrane. The infant is now 1 year old without any neurological problem. Fetoscopic laser photocoagulation of placental communicating vessels can be the procedure of choice for TRAP sequence.

A Case of Monochorionic Twin Pregnancy Complicated with Intrauterine Single Fetal Death with Successful Treatment of Intrauterine Blood Transfusion in the Surviving Fetus

We report a case of monochorionic twin pregnancy complicated with single fetal demise that received successful treatment of intrauterine transfusion for severe anemia of the surviving fetus. A single fetal demise occurred at 20 weeks of gestation and middle cerebral artery peak systolic velocity (MCA-PSV), a marker for fetal anemia, showed marked elevation in the surviving fetus. Fetal blood sampling was immediately done and severe fetal anemia (hemoglobin = 5.5 g/dl, hematocrit = 16.8%) was confirmed, and then intrauterine transfusion was performed. After transfusion, MCA-PSV rapidly decreased to the normal value and remained within normal range until delivery. A healthy 2,640 g male infant was delivered at 35 weeks of gestation without anemic status and no neurological problem was found at 1-year old. The present report supports that intrauterine rescue transfusion is a useful treatment to prevent the adverse outcome of surviving fetus in monochorionic twin pregnancy complicated with single fetal demise, and monitoring of MCA-PSV is also useful to assess anemic status of the surviving fetus.

Two cases of reversal of twin-twin transfusion syndrome diagnosed by measuring hourly fetal urine production

Reversal of twin‐twin transfusion syndrome (TTTS) is a rare complication of monochorionic pregnancy. Diagnostic criteria and satisfactory therapeutic options have not been reported. We make a suggestion of diagnosis and therapy for reversal of TTTS. We report two cases of reversal of TTTS. Measurement of the fetal urine production rate was useful for management and better comprehension of the cases. In case 1, double intrauterine fetal demise occurred before the criteria for TTTS were fulfilled, in which each fetal urine production rate reversed prior to the change of amniotic fluid volume. In case 2, elevated urine production was noted prior to progressive polyhydroamnios and congestive heart failure in the new recipient and the fetoscopic laser photocoagulation of the placental communicating vessels was performed successfully before the criteria for TTTS were fulfilled. Both infants required intensive care, but developed normally and showed no neurologic complications at 2 years after birth. Hourly fetal urine production rate was useful for immediate diagnosis of reversal of TTTS, and laser photocoagulation of the placental communicating vessels is thus a method for the correction of the fetal blood flow imbalance in cases of reversal of the donor‐recipient phenotype in TTTS.

Prenatal diagnosis and management for a large fetal cardiac tumor complicated with hydrops fetalis

Fetal cardiac tumor is a rare disease, and its prognosis varies in relation to the complications such as arrhythmia and out‐flow obstruction. Hydrops fetalis is one of severe complications that result in an unfavorable outcome. A case is presented herein of a large fetal cardiac tumor diagnosed at 28 weeks gestation. At 30 weeks gestation, the fetus complicated with hydrops fetalis because of impaired cardiac function. Increased peak systolic velocity in the ascending aorta and marked reversed flow in the ductus venosus were observed. Oral digoxin therapy was administered to the mother as a cardiotonic agent and the hydropic condition was immediately diminished. After normal delivery, the cardiac tumor gradually decreased in size and the infant developed normally, but required an antiarrhythmic drug. The case indicates that the in utero digoxin therapy could be a choice for hydrops fetalis caused by cardiac tumor.

Congenital high airway obstruction syndrome in the breech presentation managed by ex utero intrapartum treatment procedure after intraoperative external cephalic version

Congenital high airway obstruction syndrome (CHAOS) caused by laryngeal atresia was diagnosed by prenatal ultrasound in a male fetus at 26 weeks of gestation. Findings included massive ascites, subcutaneous edema, enlarged hyperechogenic lungs with diaphragmatic inversion, dilated trachea, polyhydramnios, and breech presentation. Those findings of CHAOS spontaneously returned to normal by 33 weeks of gestation. However, the placenta was localized to the anterior uterine wall. In addition, the fetal position had been breech until delivery. At 36 weeks of gestation, a planned ex utero intrapartum treatment (EXIT) procedure was performed following intraoperative external cephalic version (ECV) in which the fetus was approached from the posterior wall of the uterus. Laryngoscopy revealed the predicted laryngeal obstruction, and tracheostomy was placed. Intraoperative ECV may be a useful technique in breech presentation before EXIT procedure.

Case of pure ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin but responsive to monotherapy with weekly irinotecan

Primary ovarian squamous cell carcinoma is uncommon, and the optimal treatment strategy for this disease has not yet been established. A 71‐year‐old woman diagnosed with FIGO stage IIb pure ovarian squamous cell carcinoma underwent cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin. After the second treatment course, a recurrent mass grew rapidly, and serum tumor maker levels increased. Monotherapy with weekly irinotecan was then instituted. This second‐line chemotherapy was remarkably effective, and the patient subsequently underwent complete interval debulking surgery with a pathological complete response after the third treatment course. Weekly irinotecan is an effective choice for primary ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin.